Y. Shrike Zhang

• Ph.D.
• Assistant Professor at Harvard Medical School

Purpose Death receptor (DR)–targeted therapies offer a promising tumor cell–specific therapeutic strategy for highly malignant brain tumors, such as glioblastoma (GBM). However, whether DR-mediated cell death leads to activation of the adaptive immune system and impacts the tumor immune microenvironment (TIME) remains unknown. In this study, we exp...

Cancer metastasis begins with intravasation, where cancer cells enter blood vessels through complex interactions with the endothelial barrier. Understanding this process remains challenging due to the lack of physiologically relevant models. Here, INVADE (Intravasation‐on‐µDevice), a biomimetic microfluidic platform, is presented, enabling high‐thr...

Animal models are commonly used for drug screening before clinical trials. However, developing these models is time-consuming, and the results obtained from these models may differ from clinical outcomes due to the differences between animals and humans. To this end, 3D bioprinting offers several advantages for drug screening, such as high reproduc...

Engineered living systems (ELSs) represent purpose‐driven assemblies of living components, encompassing cells, biomaterials, and active agents, intricately designed to fulfill diverse biomedical applications. Gelatin and its derivatives have been used extensively in ELSs owing to their mature translational pathways, favorable biological properties,...

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded w...

Electrical stimulation (ES) therapy accelerates cartilage healing but faces challenges due to bulky equipment, necessitating the development of a lightweight, implantable, and biocompatible electrical stimulator for improved patient compliance and benefits. Piezoelectric materials have garnered considerable attention for their potential as self‐dri...

Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted ti...

To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambie...

Current biofabrication strategies are limited in their ability to replicate native shape-to-function relationships, that are dependent on adequate biomimicry of macroscale shape as well as size and microscale spatial heterogeneity, within cell-laden hydrogels. In this study, a novel diffusion-based microfluidics platform is presented that meets the...

With the rapid development and popularization of additive manufacturing, different technologies, including, but not limited to, extrusion-, droplet-, and vat-photopolymerization-based fabrication techniques, have emerged that have allowed tremendous progress in three-dimensional (3D) printing in the past decades. Bioprinting, typically using living...

Tumor-on-chips (ToCs) are useful platforms for studying the physiology of tumors and evaluating the efficacy and toxicity of anti-cancer drugs. However, the design and fabrication of a ToC system is not a trivial venture. We introduce a user-friendly, flexible, 3D-printed microfluidic device that can be used to culture cancer cells or cancer-derive...

Droplet‐based bioprinting has shown remarkable potential in tissue engineering and regenerative medicine. However, it requires bioinks with low viscosities, which makes it challenging to create complex 3D structures and spatially pattern them with different materials. This study introduces a novel approach to bioprinting sophisticated volumetric ob...

Expansion microscopy (ExM) is a promising technology that enables nanoscale imaging on conventional optical microscopes by physically magnifying the specimens. Here, we report the development of a strategy that enables i) on-demand labeling of subcellular organelles in live cells for ExM through transfection of fluorescent proteins that are well-re...

Tissue adhesives are promising alternatives to sutures and staples to achieve wound closure and hemostasis. However, they often do not work well on tissues that are soaked in blood or other biological fluids, and organs that are typically exposed to a variety of harsh environments such as different pH values, nonhomogeneous distortions, continuous...

Decellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have rema...

4D printing has attracted widespread attention due to its ability to fabricate complex structures capable of responding to specific stimuli. However, existing smart materials used for 4D printing, such as conventional hydrogels, liquid crystal elastomers, and shape‐memory polymers, are constrained in their ability to fulfill both mechanical ultrast...

Wound repair is a complex and dynamic process, involving stages of hemostasis, inflammation, proliferation, and remodeling. Standard methods currently used for clinical treatment of skin defects remain unsatisfying and alternative treatments have emerged including acupuncture mostly relying on the conventional needle method. It is applied sustained...

Copper−cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegrad-ability of CuHARS under diverse biological conditions, making them a viable source of essential...

Volumetric printing, an emerging additive manufacturing technique, builds objects with enhanced printing speed and surface quality by forgoing the stepwise ink-renewal step. Existing volumetric printing techniques almost exclusively rely on light energy to trigger photopolymerization in transparent inks, limiting material choices and build sizes. W...

Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microen...

Cell encapsulation within three‐dimensional hydrogels is a promising approach to mimic tissues. However, true biomimicry of the intricate microenvironment, biophysical and biochemical gradients, and the macroscale hierarchical spatial organisations of native tissues is an unmet challenge within tissue engineering. This review provides an overview o...

The human body relies on modular assembly for realizing its functions. Here the development of a bioinspired cryo(bio)printing‐based method is reported to fabricate shelf‐ready, storable modular scaffolds toward scalable tissue assembly. The mechanism lies in that the cryo(bio)printed modular scaffolds are first assembled into the final hierarchy i...

Developing a reproducible and secure supply of customizable control tissues that standardizes for the cell type, tissue architecture, and preanalytics of interest for usage in applications including diagnostic, prognostic, and predictive assays, is critical for improving our patient care and welfare. The conventionally adopted control tissues direc...

Smart biomaterials with the capacity to alter their properties in response to an outside stimulus or from within the environment around them have picked up significant attention in the biomedical community. This is primarily due to the interest in applications that may be anticipated from them in a considerable number of dynamic structures and devi...

Three-dimensional (3D) printing is an emerging technique that has shown promising success in engineering human tissues in recent years. Further development of vat-photopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components. Similarly, the development of micr...

Volumetric additive manufacturing is a novel fabrication method allowing rapid, freeform, layer-less 3D printing. Analogous to computer tomography (CT), the method projects dynamic light patterns into a rotating vat of photosensitive resin. These light patterns build up a three-dimensional energy dose within the photosensitive resin, solidifying th...

INTRODUCTION Lung cancer is the most common tumor to metastasize to the brain, as 40% of patients develop brain metastasis (BM). Once diagnosed, survival is only 6.5-10 months. A potential target to prevent BM is circulating tumor cells (CTCs). The mechanisms that mediate a CTCs adaptation to the harsh environment of circulation and BM have not bee...

Bioprinters show great promise as enablers of regenerative medicine and other biomedical engineering applications. In this work, we present a flexible and cost-effective design for a do-it-yourself bioprinter capable of printing/bioprinting gelatin methacryloyl (GelMA) and Pluronic constructs at flow rates of 0.05-0.1 mL/min and effective resolutio...

Nature abounds with micro‐architected materials containing layered multi‐material patterns that often transition within the very same monolithic piece. Fabricating these complex materials using current technologies is challenging. Multimaterial chaotic printing is presented—an extrusive printing method based on the use of chaotic advection—that can...

Microfluidic three-dimensional cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a c...

Light-based vat-polymerization bioprinting enables computer-aided patterning of 3D cell-laden structures in a point-by-point, layer-by-layer or volumetric manner, using vat (vats) filled with photoactivatable bioresin (bioresins). This collection of technologies — divided by their modes of operation into stereolithography, digital light processing...

The field of biofabrication has seen tremendous advances in the past decade. More recently, the emerging role of biofabrication in allowing faithful generation of models of human tissues in their healthy and diseased states has been demonstrated and has rapidly expanded. These biomimetic models are potentially widely applicable in a range of resear...

Encapsulated cell-based therapies for solid tumors have shown promising results in pre-clinical settings. However, the inability to culture encapsulated therapeutic cells prior to their transplantation has limited their translation into clinical settings. In this study, we created a wide variety of engineered therapeutic cells (ThC) loaded in micro...

Fibrotic tumors, such as pancreatic ductal adenocarcinoma (PDAC), are characterized for high desmoplastic reaction, which results in high intra-tumoral solid stress leading to the compression of blood vessels. These microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of therapeutics. Currently, there is a lack of...

Cholangiocarcinoma (CCA) is characterized by heterogeneous mutations and a refractory nature. Thus, the development of a model for effective drug screening is urgently needed. As the established therapeutic testing models for CCA are often ineffective, we fabricated an enabling three-dimensional (3D)-bioprinted CCA-on-a-chip model that to a good ex...

Complete skin reconstruction is a hierarchical, physiological assembly process involving healing of the epidermis, dermis, vasculature, nerves, and cutaneous appendages. To date, few works have reported complete skin regeneration, particularly lacking vascular structures and hair follicles after full skin defects. In this study, a hydrogel derived...

The role of the human intestinal tract in host-microbe interactions has been highlighted in recent years. Several 3-dimensional (3D) models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota. One challenge for 3D models is to recapitulate the low oxygen concentra...

Significance: Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep t...

While there has been considerable success in the three-dimensional bioprinting of relatively large standalone filamentous tissues, the fabrication of solid fibers with ultrafine diameters or those cannular featuring ultrathin walls remains a particular challenge. Here, an enabling strategy for (bio)printing of solid and hollow fibers whose size ran...

Bioprinting In article number 2210521, Khoon S. Lim, and co‐workers highlight a scaffolding approach to engineering blood vessels, starting from lego like construction of macro‐scale vessels to functional micro‐scale vessels. Programmable sacrificial bioinks are developed, and applied to a range of biofabrication platforms, introducing architectura...

Volumetric additive manufacturing (VAM) enables fast photopolymerization of three-dimensional constructs by illuminating dynamically evolving light patterns in the entire build volume. However, the lack of bioinks suitable for VAM is a critical limitation. This study reports rapid volumetric (bio)printing of pristine, unmodified silk-based (silk se...

Sacrificial printing allows introduction of architectural cues within engineered tissue constructs. This strategy adopts the use of a 3D‐printed sacrificial ink that is embedded within a bulk hydrogel which is subsequently dissolved to leave open‐channels. However, current conventional sacrificial inks do not recapitulate the dynamic nature of tiss...

Three‐dimensional (3D) bioprinting is driving significant innovations in biomedicine over recent years. Under certain scenarios such as in intraoperative bioprinting, the bioinks used should exhibit not only cyto/biocompatibility but also adhesiveness in wet conditions. Herein, an adhesive bioink composed of gelatin methacryloyl, gelatin, methacryl...

The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications. Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we propose a strategy that employs hydrogel microsp...

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this work reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL-37-mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide-co-lactide) (PGLA 90:10)/gelatin and poly-p-dioxanone (PDO)/gelat...

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The...

Biocompatible Conductive Inks In article number 2107099, Cunjiang Yu and co‐workers report the recent development of a conductive ink that is fully biocompatible at the cell, tissue, and organ levels. It also allows for conformal interfacing with human skin for high‐fidelity electrophysiological measurements. This cover illustrates the conformal co...

The spaceflight environment, including microgravity and radiation, may have considerable effects on the health and performance of astronauts, especially for long-duration and Martian missions. Conventional on-ground and in-space experimental approaches have been employed to investigate the comprehensive biological effects of the spaceflight environ...

Advances in biomimetic three-dimensional (3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional (2D) cell culture. Gelatin methacryloyl (GelMA) is widely used as a tissue-engineered sc...

In 3D (bio)printing, it is critical to optimize the printing conditions to obtain scaffolds with designed structures and good uniformities. Traditional approaches for optimizing the parameters oftentimes rely on the prior knowledge of the operators and tedious optimization experiments, which can be both time‐consuming and labor‐intensive. Moreover,...

Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a mol...

It is well‐known that tissue engineering scaffolds that feature highly interconnected and size‐adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting...

Chenjie Xu, Yu Shrike Zhang, Sylvie Begin and Nguyễn Thị Kim Thanh introduce the Nanoscale and Nanoscale Advances themed collection on advanced functional nanomaterials for biomedical applications.

Coaxial Extrusion In article number 2102411 by Xunwei Wu, Yu Shrike Zhang, and co‐workers, an enabling vertical‐embedded extrusion bioprinting strategy is reported by using uniaxial or coaxial nozzles, which allows formation of vertical tissue structures of homogeneous or heterogeneous properties in nature. This technique will likely bring further...

Cancer continues to be a leading cause of mortality in modern societies; therefore, improved and more reliable in vitro cancer models are needed to expedite fundamental research and anti-cancer drug development. Here, we describe the use of a miniaturized continuous stirred tank reactor (mCSTR) to first fabricate and mature cancer spheroids (i.e, d...

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD‐derived hydrogel conta...

The architecture of the colloidal photonic crystals (CPCs) is of paramount importance to their functionality and applications. Nevertheless, the realization of CPCs with arbitrarily designed, volumetrically sophisticated structures at the macroscale remains challenging. In this work, a printable CPC ink was developed. By combining this ink with a d...

PurposeThree-dimensional (3D) bioprinting offers great potentials in rebuilding tissue mimics through engineering cell-laden constructs. Recently, the unique ability of a new type of micropore-forming bioink developed by us, containing two immiscible aqueous phases of gelatin methacryloyl (GelMA) and poly(ethylene oxide) (PEO), has become attractiv...

3D Cryo‐Bioprinting A vertical 3D cryo‐bioprinting technique is reported by Yu Shrike Zhang and co‐workers in article number 2108931, which concurrently allows the user to create freestanding filamentous structures containing interconnected, anisotropic microchannels featuring gradient sizes aligned in the vertical direction, also associated with e...

Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two...

Due to poor mechanical properties of many hydrogel bioinks, conventional three-dimensional (3D) extrusion bioprinting is usually conducted based on the X-Y plane, where the deposited layers are stacked in the Z direction with or without the support of prior layers. Herein, we report a technique taking advantage of a cryoprotected bioink to enable d...

Thrombosis in the circulation system can lead to major myocardial infarction and cardiovascular deaths. Understanding thrombosis formation is necessary for developing safe and effective treatments. In this work, using digital light processing (DLP)-based 3D printing, we fabricated sophisticated in vitro models of blood vessels with internal microch...

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias d...

Bioprinting In article number 2107038, Yu Shrike Zhang and co-workers develop a (bio)printing system based on Digital Light Processing to utilize the integration of a microfluidic mixer for the generation of either continual or discrete gradients of desired (bio)inks in real time. As such, the precisely controlled gradients are composable on-the-fl...

Three-dimensional bioprinting represents promising approach for fabricating standalone and perfusable vascular conduits using biocompatible materials. Here we describe a step-by-step method by using a multichannel coaxial extrusion system (MCCES) and a blend bioink constituting gelatin methacryloyl, sodium alginate, and eight-arm poly(ethylene glyc...

Biomaterials as bioinks are essential to 3D bioprinting. Bioinks can be formulated from a broad range of naturally occurring biomaterials as well as synthetic ones, or their combinations. It is often required to tailor the bioink formulation for a specific print with desired tissue-level functions. Usually, the rheological, mechanical, and biologic...

We report 3D-printed, configurable, paper-based organ-on-paper platforms where autonomous and continuous delivery of media to engineered microtissue models is readily achieved without requiring external electrical power during device operations.

The 3D bioprinting technologies have attracted increasing attention due to their flexibility in producing architecturally relevant tissue constructs. Here, a vertical embedded extrusion bioprinting strategy using uniaxial or coaxial nozzles is presented, which allows formation of vertical structures of homogeneous or heterogeneous properties. By ad...

Microneedles (MNs) as a minimally invasive tool have drawn increasing attention recently. They possess many prominent advantages, including pain-free, self-administration, and ease-of-disposal, when compared to the traditional administration tools. This review summarizes the latest developments of the MN technology and focuses on the advanced appli...

The physical morphologies of nanoparticles, especially size and shape, always significantly influence their biological behaviors. In the past, nanoparticles with constant physical morphologies have been widely investigated and applied in tumor theranostics. With the increased in-depth knowledge of tumors and physiological microenvironments, nanopar...

One significant drawback of existing bioprinted tissues is their lack of shelf availability, caused by complications in both fabrication and storage. Here, we report a cryobioprinting strategy for simultaneously fabricating and storing cell-laden volumetric tissue constructs through seamlessly combining extrusion bioprinting and cryopreservation. T...